組蛋白賴氨酸甲基轉(zhuǎn)移酶2D （histone-lysine N-methyltransferase 2D, KMT2D）作為主要的組蛋白3第4位賴氨酸（H3K4）甲基轉(zhuǎn)移酶,在調(diào)控胚胎發(fā)育、組織分化、代謝和腫瘤抑制方面發(fā)揮重要作用。在小鼠體內(nèi),敲除Kmt2d會(huì)導(dǎo)致嚴(yán)重的心臟發(fā)育缺陷最終造成胚胎期死亡。低氧誘導(dǎo)因子-1α（hypoxia-inducible factor 1α, HIF-1α）作為調(diào)節(jié)細(xì)胞應(yīng)對(duì)低氧的關(guān)鍵轉(zhuǎn)錄因子,能夠調(diào)控多種下游基因轉(zhuǎn)錄。有相關(guān)研究揭示,表觀遺傳調(diào)控者能夠調(diào)節(jié)HIF-1α的穩(wěn)定性和活性。同樣,作為表觀遺傳調(diào)控者的組蛋白甲基轉(zhuǎn)移酶KMT2D是否參與低氧條件下HIF-1α對(duì)下游基因的調(diào)控,目前仍未知。在本研究中,觀察在Kmt2d正�；蛉狈Φ那闆r下,心肌細(xì)胞H9c2對(duì)低氧環(huán)境的應(yīng)答反應(yīng)。結(jié)果顯示,與常氧條件相比,低氧狀態(tài)下HIF-1α、組蛋白乙酰化酶P300、KMT2D及其介導(dǎo)的H3K4一甲基化（H3K4 mono-methylation, H3K4me1）的蛋白質(zhì)水平增加（P<0.05）;HIF-1α下游基因血管內(nèi)皮生長(zhǎng)因子（vascular endot... 

【文章頁(yè)數(shù)】：7 頁(yè)

【文章目錄】：
1 Materials and Methods
    1.1 Cells culture and treatment
    1.2 Nuclear extraction
    1.3 Western blot
    1.4 qRT-PCR
    1.5 ChIP-qPCR
    1.6 Gene silencing of Kmt2d
    1.7 Statistical analysis
2 Results
    2.1 Increased KMT2D, HIF-1α, P300, and H3K4me1 protein expression in H9c2 cells under hypoxic condition
    2.2 Enhanced mRNA expression of Vegf and enrichment of H3K4me1 and H3K27ac on Vegf promoter in H9c2 cells under hypoxic condition
    2.3 Knockdown of Kmt2d reduced the accumulation of HIF-1α and the expression of Vegf under hypoxic condition
3 Discussion



本文編號(hào)：3665341